Optically active halohydrin compounds, such as 2-chloro-1-phenylethanol, are known useful as intermediates for pharmaceutical or agricultural chemicals. Known techniques for producing these halohydrin compounds include a process comprising asymmetrically reducing an α-haloketone compound such as acetophenone by microbial cells (International Publication WO92/01804) and a process comprising asymmetrically reducing a similar α-haloketone compound through hydroboration using oxaborolidines as a catalyst (U.S. Pat. No. 5,495,054). The process involving use of microbial cells requires a large quantity of a solvent for dissolving the substrate, which cannot be necessarily seen as fit for industrial production. The process using oxaborolidines as a catalyst cannot be seen as favorable for industrial application from the aspect of safety because of toxicity of diborane used as a reducing agent. Accordingly, a process of preparing an optically active halohydrin compound which is efficient and suited to industrial application has been sought for.
Several processes are known for obtaining optically active benzyl alcohols through asymmetric reduction of acetophenones.
For example, International Publication WO97/20789 discloses that asymmetric reduction of acetophenone in the presence of a catalyst composed of an Ru complex and an optically active amine derivative gives an optically active 1-methylbenzyl alcohol. WO98/42643 and JP-A-11-335385 teach asymmetric reduction of acetophenone using an Rh complex in place of the Ru complex to prepare an optically active 1-methylbenzyl alcohol. J. Org. Chem., 1999, 64, 2186-2187 reports a process of preparing optically active 1-methylbenzyl alcohol by asymmetric reduction of acetophenone in the presence of a catalyst comprising an Rh complex or an Ir complex and N-(p-toluenesulfonyl)-cyclohexanediamine.
These processes feature asymmetric hydrogen transfer reduction using transition metal complex catalysts. Substituting the acetophenones with the above-mentioned α-haloketone compounds such as 2-chloroacetophenone as a reaction substrate in any of these processes results in no reaction progress or extremely low yields as reported in Synlett., 1999, 1615-1617. WO01/17962 discloses asymmetric hydrogen transfer reduction of 2-chloro-3′-nitroacetophenone by using a ruthenium catalyst. However, the process may not be necessarily regarded satisfactory for industrial production in view of optical yield and amount of catalyst.
It is an object of the present invention to provide a process of preparing an optically active halohydrin compound from an α-haloketone compound in high yield and high optical yield.